Treatment of pharmacoresistant epilepsy

Abstract

Methods for treating epilepsy, particularly a pharmacoresistant epilepsy, include administering to a subject in need thereof a compound of a class including propynones, propynals, propynols, propynes, propenones, amides, quinolinones, naphthyridinones, thiopyranoxides, pyrazolopyridines, and indazoles. The compounds have a general formula R 1 —X—C≡C—R 2 , where is selected from C═O, CH—OH, CH 2 and C═N—, with the proviso that if X is C═N—, the nitrogen is bound to a nitrogen atom of an R 1 substituent, where R 1 is hydrogen, alkyl, aromatic, or heteroaromatic, and where R 2 is phenyl, substituted phenyl, alkyl, or cycloalkyl.

1 - 31 . (canceled) 
     
     
         32 . A method for treating epilepsy, the method comprising administering to a subject in need thereof a compound of formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt of the compound of formula (I) in the form of a hydrate, solvate, or complex, where in formula (I):
 X is selected from C═O, CH—OH, CH 2  and C═N—, with the proviso that if X is C═N—, the nitrogen is bound to a nitrogen atom of an R 1  substituent; 
 R 1  is selected from the group consisting of:
 hydrogen, methyl, or a linear or branched C 2 -C 4  alkyl; 
 an aromatic or aliphatic 5 membered ring, optionally comprising heteroatoms and/or optionally comprising further substituents; 
 an aromatic or aliphatic 6 membered ring, optionally comprising one or more heteroatoms and/or optionally comprising further substituents; and 
 a double 6 membered ring, wherein one or both rings are aromatic and optionally comprising one or more hetero atoms, and/or optionally comprising further substituents; and 
 
 R 2  is selected from the group consisting of:
 phenyl, optionally substituted with OH, OCH 3 , ethyl, halomethyl, one or more halogens, or with a linear or branched C 2 -C 8  alkyl, where the C 2 -C 8  alkyl is optionally further substituted with ═O or where a carbon atom in the C 2 -C 8  alkyl is replaced with a halogen; and 
 a linear or branched C 1 -C 10  alkyl in which a carbon atom is optionally replaced with a Si atom; and 
 a C 3 -C 6  cycloalkyl. 
 
 
       
     
     
         33 . The method of  claim 32 , wherein R 1  is phenyl, optionally substituted with —OH, —NO 2 , —NH 2 , —OCH 3 , —OCH 2 CH 3 , —CH 2 —NH 2 , —CH 2 —CH 2 —NH 2 , —F, or —Cl. 
     
     
         34 . The method of  claim 32 , wherein R 1  is phenyl, substituted with a C 1 -C 6 , or C 1 -C 4  alkyl wherein carbon is optionally replaced by oxygen and/or optionally comprises one or more —OH or ═O substituents. 
     
     
         35 . The method of  claim 32 , wherein R 1  is phenyl, substituted with an aliphatic 6 membered ring, with optionally 1 or 2 hetero atoms. 
     
     
         36 . The method of  claim 32 , wherein R 1  is an aromatic 5 membered ring, optionally comprising a sulfur heteroatom, or optionally comprising 1 or 2 nitrogen atoms. 
     
     
         37 . The method of  claim 32 , wherein X is C═O, CH—OH, or CH 2 . 
     
     
         38 . The method of  claim 32 , wherein X is CH—OH, wherein R 1  is phenyl and R 2  is a phenyl substituted with methyl or a linear or branched C 2  to C 6  alkyl. 
     
     
         39 . The method of  claim 32 , wherein the compound is rac-3-(4-(tert-butyl)phenyl)-1-phenylprop-2-yn-1-ol. 
     
     
         40 . The method of  claim 32 , wherein X is C═N—, and the nitrogen of C═N— is bound to a nitrogen atom of R 1 . 
     
     
         41 . The method of  claim 32 , wherein X is C═N—, and wherein the compound comprises a pyrazolo [3,4-b] pyridine moiety or a indazole moiety. 
     
     
         42 . The method of  claim 32 , wherein the compound is 3-((3-chlorophenyl)ethynyl)-1H-pyrazolo[3,4-b]pyridine. 
     
     
         43 . The method of  claim 32 , wherein the epilepsy is a treatment-resistant epilepsy. 
     
     
         44 . A compound having formula (I): 
       
         
           
           
               
               
           
         
         where:
 X is selected from C═O, CH—OH, —CH 2  or C═N—, with the proviso that if X is C═N—, the nitrogen of the C═N— is bound to a nitrogen atom of an R 1  substituent; 
 R 1  is selected from the group consisting of:
 hydrogen, methyl or a linear or branched C 2 -C 4  alkyl; 
 an aromatic or aliphatic 5 membered ring, optionally comprising heteroatoms and/or optionally comprising further substituents; 
 an aromatic or aliphatic 6 membered ring, optionally comprising one or more heteroatoms and/or optionally comprising further substituents; and 
 a double 6 membered ring, wherein one or both rings are aromatic and optionally comprising one or more hetero atoms, and/or optionally comprising further substituents, and 
 
 R 2  is selected from the group consisting of:
 phenyl, optionally further substituted with —OH, —OCH 3 , ethyl, halomethyl, one or more halogens, or with a linear or branched C 2 -C 8  alkyl, wherein the C 2 -C 8  alkyl is optionally further substituted with ═O or wherein a carbon atom in the C 2 -C 8  alkyl is replaced with a halogen; 
 a linear or branched C 1 -C 10  alkyl, in which a carbon atom is optionally replaced with a Si atom; and 
 a C 3 -C 6  cycloalkyl. 
 
 
       
     
     
         45 . The compound of  claim 44 , wherein R 1  is phenyl, optionally substituted with —OH, —NO 2 , —NH 2 , —OCH 3 , —OCH 2 CH 3 , —CH 2 —NH 2 , —CH 2 —CH 2 —NH 2 , —F, or —Cl. 
     
     
         46 . The compound of  claim 44 , wherein R 1  is phenyl, substituted with a C 1 -C 6 , or C 1 -C 4  alkyl wherein a carbon atom is optionally replaced by oxygen and/or optionally comprises one or more —OH or ═O substituents. 
     
     
         47 . The compound of  claim 44 , wherein R 1  is phenyl, substituted with aliphatic 6 membered ring, with optionally 1 or 2 hetero atoms. 
     
     
         48 . The compound of  claim 44 , wherein R 1  is an aromatic 5 membered ring, optionally comprising a sulfur heteroatom, or optionally 1 or 2 nitrogen atoms. 
     
     
         49 . The compound of  claim 44 , wherein X is selected from —C═O, —CH—OH, or —CH 2 . 
     
     
         50 . The compound of  claim 44 , wherein X is CH—OH, and wherein R 1  is phenyl and R 2  is a phenyl substituted with methyl or a linear or branched C 2 -C 6  alkyl. 
     
     
         51 . The compound of  claim 44 , wherein the compound is rac-3-(4-(tert-butyl)phenyl)-1-phenylprop-2-yn-1-ol. 
     
     
         52 . The compound of  claim 44 , wherein X is C═N—, and the nitrogen of C═N— is bound to R 1  via a nitrogen atom of a substituent on a phenyl or pyridyl moiety. 
     
     
         53 . The compound of  claim 44 , wherein X is C═N— and wherein the compound comprises a pyrazolo [3,4-b] pyridine moiety or a indazole moiety. 
     
     
         54 . The compound of  44 , wherein the compound is 3-((3-chlorophenyl)ethynyl)-1H-pyrazolo[3,4-b]pyridine.